Chinese researchers have developed a new technology that sheds light on why some metastatic cancers resist immunotherapy and how that resistance might be overcome.
Metastasis, the spread of cancer to other parts of the body, is the leading cause of cancer-related deaths. As tumors spread, they form a surrounding “microenvironment” — a complex ecosystem that can either support or hinder the immune system’s attack.
Scientists have found that certain genetic mutations allow tumors to reshape this environment, creating barriers that keep cancer-killing immune cells out. To better understand this process, researchers led by Wang Guangchuan at the Center for Excellence in Molecular Cell Science under the Chinese Academy of Sciences developed a new platform called CLIM-TIME. The system maps immune cells inside metastatic tumors and links their distribution to specific genetic changes.
Analyzing 391 tumor-suppressor gene alterations, the team identified seven distinct microenvironment types. Tumors with defects in DNA repair genes tended to attract immune cells and respond better to immunotherapy. In contrast , for tumors with gene mutations leading to activation of the YAP pathway, there are fewer T cells in the tumor environment, and show poor responses.
Further investigation revealed high levels of collagen in these resistant tumors. The dense collagen acted as a physical barrier, preventing T cells from entering. By blocking an enzyme called LOXL2 — which helps maintain collagen structure — researchers were able to reduce this barrier in animal models, allowing immune cells to infiltrate tumors and significantly improving treatment response.
Using machine learning, the team also developed a model based on 30 genetic markers to help predict how patients might respond to immunotherapy.
The findings, published in“Cell”on February 12, offering a new strategy for tackling treatment resistance in metastatic cancer.
原载于Community2026-02-15
作者：Li Qian
